Host miR-146a-3p Facilitates Replication of Infectious Hematopoietic Necrosis Virus by Targeting WNT3a and CCND1.

Infectious hematopoietic necrosis virus (IHNV) is a serious pathogen that causes great economic loss to the salmon and trout industry. Previous studies showed that IHNV alters the expression patterns of splenic microRNAs (miRNAs) in rainbow trout. Among the differentially expressed miRNAs, miRNA146a-3p was upregulated by IHNV. However, it is unclear how IHNV utilizes miRNA146a-3p to escape the immune response or promote viral replication. The present study suggested that one multiplicity of infection (MOI) of IHNV induced the most significant miR-146a-3p expression at 1 day post infection (dpi). The upregulation of miR-146a-3p by IHNV was due to viral N, P, M, and G proteins and relied on the interferon (IFN) signaling pathway. Further investigation revealed that Wingless-type MMTV integration site family 3a (WNT3a) and G1/S-specific cyclin-D1-like (CCND1) are the target genes of miRNA-146a-3p. The regulation of IHNV infection by miRNA-146a-3p is dependent on WNT3a and CCND1. MiRNA-146a-3p was required for the downregulation of WNT3a and CCND1 by IHNV. Moreover, we also found that WNT3a and CCND1 are novel proteins that induce the type-I IFN response in RTG-2 cells, and both of them could inhibit the replication of IHNV. Therefore, IHNV-induced upregulation of miRNA-146a-3p promotes early viral replication by suppressing the type-I IFN response by targeting WNT3a and CCND1. This work not only reveals the molecular mechanism of miRNA-146a-3p during IHNV infection but also provides new antiviral targets for IHNV.

Chinese medicine in the treatment of non-alcoholic fatty liver disease based on network pharmacology: a review.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by abnormalities in hepatic fat deposition, the incidence of which has been increasing year by year in recent years. It has become the largest chronic liver disease globally and one of the important causes of cirrhosis and even primary liver cancer formation. The pathogenesis of NAFLD has not yet been fully clarified. Modern medicine lacks targeted clinical treatment protocols for NAFLD, and most drugs lack efficacy and have high side effects. In contrast, Traditional Chinese Medicine (TCM) has significant advantages in the treatment and prevention of NAFLD, which have been widely recognized by scholars around the world. In recent years, through the establishment of a "medicine-disease-target-pathway" network relationship, network pharmacology can explore the molecular basis of the role of medicines in disease prevention and treatment from various perspectives, predicting the pharmacological mechanism of the corresponding medicines. This approach is compatible with the holistic view and treatment based on pattern differentiation of TCM and has been widely used in TCM research. In this paper, by searching relevant databases such as PubMed, Web of Science, and Embase, we reviewed and analyzed the relevant signaling pathways and specific mechanisms of action of single Chinese medicine, Chinese medicine combinations, and Chinese patent medicine for the treatment of NAFLD in recent years. These related studies fully demonstrated the therapeutic characteristics of TCM with multi-components, multi-targets, and multi-pathways, which provided strong support for the exact efficacy of TCM exerted in the clinic. In conclusion, we believe that network pharmacology is more in line with the TCM mindset of treating diseases, but with some limitations. In the future, we should eliminate the potential risks of false positives and false negatives, clarify the interconnectivity between components, targets, and diseases, and conduct deeper clinical or experimental studies.

ABA-importing transporter (AIT1) synergies enhances exogenous ABA minimize heavy metals accumulations in Arabidopsis.

Exogenous abscisic acid (ABA) presents a novel approach to mitigate heavy metal (HM) accumulation in plants, yet its efficacy against multiple HMs and potential enhancement methods remain underexplored. In this study, we demonstrated that the exogenous ABA application simultaneously decreased Zn, Cd and Ni accumulation by 22-25 %, 27-39 % and 60-62 %, respectively, in wild-type (WT) Arabidopsis. Conversely, ABA reduced Pb in shoots but increased its root concentration. ABA application also modulated the expression of HM uptake genes, inhibiting IRT1, NRAMP1, NRAMP4, and HMA3, and increasing ZIP1 and ZIP4 expressions. Further analysis revealed that overexpressing the ABA-importing transporter (AIT1) in plants intensified the reduction of Cd, Zn, and Ni, compared to WT. However, the inhibitory effect of exogenous ABA on Pb accumulation was mitigated in shoots with higher AIT1 expression. Furthermore, HMs-induced growth inhibition and the damage to photosynthesis were also alleviated with ABA treatment. Conclusively, AIT1's synergistic effect with ABA effectively reduces Cd, Zn and Ni accumulation, offering a synergistic approach to mitigate HM stress in plants.

Liver cirrhosis: current status and treatment options using western or traditional Chinese medicine.

Liver cirrhosis arises from liver fibrosis and necroinflammation caused by various mechanisms of hepatic injury. It is a prevalent condition in clinical practice characterized by hepatocellular dysfunction, portal hypertension, and associated complications. Despite its common occurrence, the etiology and pathogenesis of liver cirrhosis remain incompletely understood, posing a significant health threat. Effective prevention of its onset and progression is paramount in medical research. Symptoms often include discomfort in the liver area, while complications such as sarcopenia, hepatic encephalopathy, ascites, upper gastrointestinal bleeding, and infection can arise. While the efficacy of Western medicine in treating liver cirrhosis is uncertain, Chinese medicine offers distinct advantages. This review explores advancements in liver cirrhosis treatment encompassing non-pharmacological and pharmacological modalities. Chinese medicine interventions, including Chinese medicine decoctions, Chinese patent medicines, and acupuncture, exhibit notable efficacy in cirrhosis reversal and offer improved prognoses. Nowadays, the combination of Chinese and Western medicine in the treatment of liver cirrhosis also has considerable advantages, which is worthy of further research and clinical promotion. Standardized treatment protocols based on these findings hold significant clinical implications.

Application of network pharmacology in traditional Chinese medicine for the treatment of digestive system diseases.

With the general improvement in living standards in recent years, people's living habits, including their dietary habits, have changed. More people around the world do not follow a healthy diet, leading to an increase in morbidity and even mortality due to digestive system diseases, which shows an increasing trend every year. The advantage of traditional Chinese medicine (TCM) in treating digestive system diseases is evident. Consequently, the mechanisms of action of single Chinese herbs and compound Chinese medicines have become the focus of research. The research method of the network pharmacology system was highly consistent with the holistic concept of TCM, and provided a new perspective and theoretical basis for basic research on digestive system diseases. This article summarizes the common databases currently used in research on TCM. It also briefly introduces the basic methods and technologies of network pharmacology studies. It also summarizes the advancements of network pharmacology technology through a comprehensive literature search on PubMed. Based on this analysis, we further explored the role of TCM in treating digestive system diseases, including chronic gastritis, gastric cancer, ulcerative colitis, and liver cirrhosis. This study provides new ideas and references for treating digestive system diseases with TCM in the future and serves as a reference for relevant researchers.